Serotonergic

N. N. Osborne (ed.), Biology of Serotonergic Transmission, John Wiley. Chichester, UK, 1982. 

Unlike aniracetam, pramiracetam does not appear to interact with dopaminergic, serotonergic, or adrenergic neurotransmission (72). The agent inhibits prolylendopeptidase in certain brain areas, but its inhibition constant, iC, is only 11 ]lM (69). The absence or weak activity of this compound with various neuronal systems appears to make it less likely to be of significant therapeutic value than other members of this class of agents. 

Serotonin is a key transmitter in CNS function. Altered serotonergic function has been implicated in many CNS disorders including depression, feeding behavior, sleep disorders, schizophrenia, and Alzheimer s disease. 

Correlation between clinical effectiveness and receptor affinities, however, can be seen with other receptors in addition to the dopamine D2 receptor. These include other dopaminergic receptors, as well as noradrenergic and serotonergic receptors. For example, most antipsychotics also have high affinity for a -adrenoceptors and 5-HT2 receptors (225). Some antipsychotics have been shown to be selective for the adrenoceptor versus the a -adrenoceptor, for example, spiperone [749-02-0] (226) and risperidone (61) (221]... 

Monoamine oxidase (MAO) inactivates serotonergic and catecholaimnergic neurotransmitters MAO (A and B) inhibitors exhibit mood elevatmg properties 5-Fluoro-Ot-methyltryptamine 19) is an important MAO A-seleUive inhibitor In the treatment of certam depressive illnesses, 4-fluorotranylcypromine (20b) is 10 tunes more potent than the parent tranylcypromme (TCP, 20a) The enhanced m vivo activity may be due to increased lipophihcity at20b and/or to blockade of metabohc para hydroxylation [52]... 

Esters of tropine have a venerable place in medicinal chemistry. One such compound, cocaine, the object of some current interest, was the natural product lead which led eventually to most of today s local anesthetics. A distantly related analogue is prepared by reaction of tropine (132) with 3,5-dimethylbenzoyl chloride. This leads to an ester structurally related to another ]ii ominent natural product, atropine (133). The product, tropanaerin (134), is described as an iinti.serotonergic agent intended for antimigraine use [34]. 

SERT, 5HTT (SLC6A4) 5HT = serotonin -1 CNS serotonergic neurons (emanate from raphe nuclei) platelets, smooth muscle, intestine ... 

DAT is predominantly expressed by dopaminergic brain neurons, NET by noradrenergic neurons in the central and peripheral nervous system, and SERT is restricted to the axons of serotonergic neurons, which originate in the raphe nuclei and innervate numerous higher brain regions therefore SERT is widely distributed in the brain. Outside the brain, 5HT transport can be measured on non-neuronal cells (e.g. platelets, lympho-blastoid cells and smooth muscle cells) most of the 5HT appearing in the circulation is taken up by platelets. 

The raphe nuclei are a cluster of nuclei found in the brainstem, where they are located in the medial portion of the formatio reticularis, the raphe. (The raphe is the junction of the left and right brainstem hemisphere, hence the name raphe=seam). Serotonergic nerve cells in the CNS originate from the raphe nuclei, i.e., their rostral portion, and because of their wide-ranging projections appear to supply serotonin (5HT) to the rest of the brain. 

Dundon W, Lynch KG, Pettinati HM, et al Treatment outcomes in type A and B alcohol dependence 6 months after serotonergic pharmacotherapy. Alcohol Clin Exp Res 28 1065-1073, 2004... 

Tollefson GD, Montague-Clouse J, Tollefson SL Treatment of comorbid generalized anxiety in a recently detoxified alcohol population with a selective serotonergic drug (buspirone). J Clin Psychopharmacol 12 19-26, 1992... 

Serotonergic agents Ondansetron, ritanserin, buspirone Large controlled studies are not encouraging. 

Although the exact mechanisms of action of LSD and tryptamine-related compounds are incompletely understood (Freedman 1987), there is convincing evidence relating the psychotomimetic effects of these substances to serotonergic transmission in the brain (Davis 1987 Freedman 1987 McCall 1986 Nichols 2004). An antagonism of 5-HT in the rat brain is sufficient to cause a fourfold decrease in the threshold dose ofLSD (Appel and Freedman 1964). 

The mode of action of the amphetamine derivatives MDA and MDMA seems to be dissimilar, with MDMA possessing mescaline-like psychoactive properties. MDMA demonstrates greater serotonergic effects than does the more amphetamine-like MDA. 

As a result of the neurochemical changes caused by MDMA, there is significant, observable functional impairment as well. These impairments occur in areas of the brain that have high concentrations of serotonergic neurons. Most notably affected are cognition and memory. Studies have shown decreases... 

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